Using human APOE knock-in mice, we found that APOE genotype affected pre-synaptic components in normal brain. Specifically, APOE-ε4 TR mice had decreased glutaminase levels and increased levels of the vesicular glutamate transporter VGLUT1. Using high-frequency 13C/1H nuclear magnetic resonance spectroscopy, we found that APOE-ε4TR mice have decreased production of glutamate and increased levels of glutamine.